Publication: Propil paraben ve valproik asitin embriyonel dönemde gelişim üzerine etkilerinin karşılaştırılması
Abstract
Amaç: Bu çalışmada propil paraben (PP) ve valproik asitin (VPA) ayrı ayrı ve birlikte maruziyetleri biyokimyasal ve moleküler düzeyde incelenerek zebra balığı embriyolarında VPA ile indüklenen otizm spektrum bozukluğu (OSB) ile ilişkisinin araştırılması amaçlanmıştır. Gereç ve yöntem: Zebra balığı embriyolarına fertilizasyondan sonraki 24., 48. ve 72. saatlerde ölümcül olmayan dozlarda PP, VPA ve VPA+PP maruziyetleri yapılmış ve oksidan-antioksidan parametreler ve asetilkolinesteraz (AChE) aktivitesi değerlendirilmiştir. Görülen malformasyonlar kaydedilmiş ve lokomotor aktivite testi yapılmıştır. RT-PCR ile OSB ile ilgili seçilen gen aktivitelerinin ekspresyonları incelenmiştir. Bulgular: PP, VPA ve VPA+PP maruziyet dozlarında pigmentasyon kaybı, besin kesesi ödemi, optik vezikül bozukluğu, perikardiyal ödem ve aksiyel deformasyon görülmüştür. Tüm maruziyet gruplarında kontrol grubuna kıyasla lokomotor aktivitede azalma, lipid peroksidasyonda, nitrik oksit ve glutatyon-s-transferaz aktivitelerinde artma, süperoksit dismutaz ve AChE aktivitesinde ise anlamlı azalma görülmüştür. Maruziyet gruplarında shank3a, tscb1 ve bdnf gen ifadeleri azalırken eif4eb ve adsl genlerinin ifadeleri artmıştır. Sonuç : Maruziyet gruplarının tümünde oksidan ve antioksidan sistem olumsuz yönde etkilenmiş, gelişim geriliği ve malformasyonlar yanında otizm ile ilgili gen ifadelerinde değişiklikler görülmekle beraber bu etkiler en fazla VPA++PP grubunda gözlenmiştir.
Objective: In this study, by investigating the individual and combined effects of propyl paraben (PP) and valproic acid (VPA) exposures at the biochemical and molecular level; the relationship between PP and VPA-induced autism spectrum disorder (ASD) was aimed to be revealed in zebrafish embryos. Material and methods: Non-lethal doses of PP, VPA and VPA+PP were exposed to zebrafish embryos at 24, 48, and 72 hours after fertilization, and oxidant & antioxidant parameters and acetylcholinesterase (AChE) activity were evaluated. Observed malformations were recorded and a locomotor activity test was performed. Expressions of selected gene activities related to ASD were examined by RT-PCR. Results: Loss of pigmentation, yolk sac edema, optic vesicle defects, pericardial edema, and axial deformation were observed at exposure doses of PP, VPA, and VPA+PP. A decrease in locomotor activity, an increase in lipid peroxidation, nitric oxide and glutathione-s-transferase activities, and a significant decrease in superoxide dismutase and AChE activities were observed in all exposure groups compared to the control group. While shank3a, tscb1, and bdnf gene expressions decreased in exposure groups, eif4eb and adsl gene expressions increased. Conclusion: Exposure to PP, VPA, and VPA+PP adversely affected the oxidant and antioxidant system, and changes in gene expressions related to autism were observed as well as developmental delay and malformations. These effects were most common in the VPA+PP group.
Objective: In this study, by investigating the individual and combined effects of propyl paraben (PP) and valproic acid (VPA) exposures at the biochemical and molecular level; the relationship between PP and VPA-induced autism spectrum disorder (ASD) was aimed to be revealed in zebrafish embryos. Material and methods: Non-lethal doses of PP, VPA and VPA+PP were exposed to zebrafish embryos at 24, 48, and 72 hours after fertilization, and oxidant & antioxidant parameters and acetylcholinesterase (AChE) activity were evaluated. Observed malformations were recorded and a locomotor activity test was performed. Expressions of selected gene activities related to ASD were examined by RT-PCR. Results: Loss of pigmentation, yolk sac edema, optic vesicle defects, pericardial edema, and axial deformation were observed at exposure doses of PP, VPA, and VPA+PP. A decrease in locomotor activity, an increase in lipid peroxidation, nitric oxide and glutathione-s-transferase activities, and a significant decrease in superoxide dismutase and AChE activities were observed in all exposure groups compared to the control group. While shank3a, tscb1, and bdnf gene expressions decreased in exposure groups, eif4eb and adsl gene expressions increased. Conclusion: Exposure to PP, VPA, and VPA+PP adversely affected the oxidant and antioxidant system, and changes in gene expressions related to autism were observed as well as developmental delay and malformations. These effects were most common in the VPA+PP group.